Brigman Jonathan L, Ihne Jessica, Saksida Lisa M, Bussey Timothy J, Holmes Andrew
Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse, NIH Rockville, MD, USA.
Front Behav Neurosci. 2009 Feb 23;3:2. doi: 10.3389/neuro.08.002.2009. eCollection 2009.
Subchronic treatment with the psychotomimetic phencyclidine (PCP) has been proposed as a rodent model of the negative and cognitive/executive symptoms of schizophrenia. There has, however, been a paucity of studies on this model in mice, despite the growing use of the mouse as a subject in genetic and molecular studies of schizophrenia. In the present study, we evaluated the effects of subchronic PCP treatment (5 mg/kg twice daily x 7 days, followed by 7 days withdrawal) in C57BL/6J mice on (1) social behaviors using a sociability/social novelty-preference paradigm, and (2) pairwise visual discrimination and reversal learning using a touchscreen-based operant system. Results showed that mice subchronically treated with PCP made more visits to (but did not spend more time with) a social stimulus relative to an inanimate one, and made more visits and spent more time investigating a novel social stimulus over a familiar one. Subchronic PCP treatment did not significantly affect behavior in either the discrimination or reversal learning tasks. These data encourage further analysis of the potential utility of mouse subchronic PCP treatment for modeling the social withdrawal component of schizophrenia. They also indicate that the treatment regimen employed was insufficient to impair our measures of discrimination and reversal learning in the C57BL/6J strain. Further work will be needed to identify alternative methods (e.g., repeated cycles of subchronic PCP treatment, use of different mouse strains) that reliably produce discrimination and/or reversal impairment, as well as other cognitive/executive measures that are sensitive to chronic PCP treatment in mice.
精神分裂症的拟精神病药物苯环利定（PCP）亚慢性治疗已被提议作为该疾病阴性症状及认知/执行功能症状的啮齿动物模型。然而，尽管小鼠在精神分裂症的基因和分子研究中作为实验对象的使用越来越多，但针对该模型在小鼠中的研究却很少。在本研究中，我们评估了C57BL/6J小鼠亚慢性PCP治疗（5毫克/千克，每日两次，共7天，随后停药7天）对以下方面的影响：（1）使用社交性/社会新奇偏好范式评估社交行为；（2）使用基于触摸屏的操作性系统评估成对视觉辨别和逆向学习。结果显示，相对于无生命刺激，亚慢性接受PCP治疗的小鼠对社交刺激的访问次数更多（但与之相处的时间并未增加），并且相对于熟悉的社交刺激，对新的社交刺激的访问次数更多，且用于探究的时间更长。亚慢性PCP治疗对辨别或逆向学习任务中的行为没有显著影响。这些数据促使我们进一步分析小鼠亚慢性PCP治疗在模拟精神分裂症社交退缩成分方面潜在的效用。它们还表明，所采用的治疗方案不足以损害我们对C57BL/6J品系小鼠辨别和逆向学习的测量。需要进一步开展工作，以确定能够可靠地产生辨别和/或逆向学习障碍的替代方法（例如，亚慢性PCP治疗的重复周期、使用不同的小鼠品系），以及对小鼠慢性PCP治疗敏感的其他认知/执行功能指标。
